General principles which govern intra- and intermolecular interactions and resultant function of proteins and peptide-protein complexes have been studied for neurophysin-neuropeptide hormone complexes as well as for several related peptides and proteins. Molecular recognition by peptides and proteins underlies essentially all biological functions of these substances. The increasingly well-developed description of protein and peptide structures to atomic resolution has emphasized the importance of understanding surface organization and dynamics in defining structural bases of function. In one aspect of the current project, this issue has been addressed for the neurophysins and neuropeptide hormones, which make self-associating peptide-protein complexes in neurosecretory granules that act as granular storage forms for the polypeptides. The nature and structural interrelationships between the self-association and hormone binding surfaces in neurophysins that give rise to cooperative complexes (marked by quaternary enhancement) have been studied. Organization of the self-association surface from residues common to all studies human and bovine neurophysins and the tight structural linkage between this surface and that for hormone binding has been evaluated by quantitative affinity chromatography and photoaffinity labelling. Separately, the thesis that the structural framework of a polypeptide orients a limited set of interacting groups into structural elements for surface recognition has been verified by studying the effect of synthetic sequence modeling of ribonuclease S-peptide on forming functional ribonuclease-S. Several viable S-peptide variants of simplified sequence have been made and evaluated by both solution characterization and high resolution X-ray diffraction analysis. In addition, the way in which intramolecular domains participate in folding and stabilization has been evaluated in a study of large fragments of the protease thermolysin. The structural stability of fragments for the C-terminal third of the protein has been evaluated spectroscopically and immunochemically. The results suggest a role for domains in forming intramolecular inter-domain surface contacts to stabilize overall native protein structure.